1. Changes in fetal cardiac geometry with gestation; implications for 3- and 4-dimensional (3D/4D) fetal echocardiography. Examination of the fetal heart using two-dimensional ultrasound requires the use of conventional sonographic planes. These planes can be obtained with 3D and 4D ultrasound using novel algorithms. However, these algorithms assume that the spatial relationships among cardiac chambers and great vessels are constant throughout gestation. This year, the Branch performed a cross-sectional study by reviewing 3D/4D volume-data sets from 85 healthy fetuses obtained between 12 and 41 weeks of gestation. The following parameters were measured: 1) the angle between the ductal arch and fetal thoracic aorta; 2) the angle between the ductal arch and aortic arch; and 3) the mean angle between left outflow tract and main pulmonary artery, as seen in the short axis of the heart. The result of these analyses demonstrated that the angle between the ductal arch and fetal thoracic aorta decreased with gestational age. In contrast, the angle between the ductal and aortic arch, and the mean angle between the left outflow tract and the short axis of the heart increased with gestational age. These findings suggest that there are significant changes in fetal cardiac geometry with advancing gestational age and propose that algorithms for 3D/4D fetal echocardiography may need to be modified to address these changes with advancing gestation.[unreadable] [unreadable] 2. The role of the sagittal view of the ductal arch in the prenatal diagnosis of conotruncal anomalies with 4D ultrasonography. Conotruncal anomalies represent one fifth of all congenital heart defects diagnosed prenatally. However, the spatial relationship of the great vessels is incorrectly defined in about 20% of these cases. The sagittal view of the ductal arch is considered a standard ultrasonographic view in fetal echocardiography, and can be easily visualized with 4D ultrasonography using an algorithm developed by our Branch. The current study used volume data sets, acquired with the spatiotemporal image correlation (STIC) technique, from fetuses with and without confirmed conotruncal anomalies. The visualization rate of the sagittal view of the ductal arch was significantly lower in fetuses with conotruncal anomalies than in fetuses without abnormalities and in fetuses with other CHDs. Moreover, absence of visualization of the sagittal view of the ductal arch was associated with a likelihood ratio of 9.44 for a conotruncal anomaly. Visualization of the sagittal view of the ductal arch may play an important role in the screening and prenatal diagnosis of conotruncal anomalies using 4D ultrasonography.[unreadable] [unreadable] 3. The combination of ultrasound and biochemical markers for the identification of patients at risk for the development of preeclampsia. A prospective cohort study was conducted to examine the relationship between abnormal uterine artery Doppler velocimetry (UADV), between 22 and 26 weeks of gestation, and plasma concentrations of Placental Growth Factor (PlGF) in 3,348 pregnant women. An abnormal UADV and maternal plasma PlGF of <280 pg/mL were independent risk factors for the occurrence of preeclampsia, severe preeclampsia, early onset preeclampsia, and SGA without preeclampsia. Of note, the combination of abnormal UADV and maternal plasma PlGF of <280 pg/mL was associated with an odds ratio (OR) of 43.8 for the development of early onset preeclampsia (<34 weeks), an OR of 37.4 for the development of severe preeclampsia, and an OR of 8.6 for the development of preeclampsia. Thus, a combination of abnormal UADV in the second trimester of pregnancy and a low concentration of PlGF in maternal blood can identify a subgroup of patients who are at a very high risk of developing early onset and/or severe preeclampsia. These patients may be candidates for future randomized clinical trials.[unreadable] [unreadable] 4. Differential prenatal diagnosis of congenital diaphragmatic eventration and congenital diaphragmatic hernia. The prognosis and postnatal management of congenital diaphragmatic eventration and congenital diaphragmatic hernia are different. Thus, the accurate prenatal diagnosis of these two congenital anomalies is important for patient management. We have recently reported that a higher proportion of fetuses with diaphragmatic eventration had associated pleural and pericardial effusions compared with those fetuses with diaphragmatic hernia. Thus, the presence of pleural and/or pericardial effusion in patients with diaphragmatic defects should raise the index of suspicion for the diagnosis of congenital diaphragmatic eventration. This may be helpful in the differential diagnosis of these two conditions.[unreadable] [unreadable] 5. Evaluation of fetal brain sulcation with 3D ultrasound. The evaluation of fetal cerebral cortex sulcation is important for the prenatal diagnosis of neuronal migration disorders. Although abnormal sylvian fissure morphologic features are frequently observed in these conditions, the diagnosis of an abnormal sylvian fissure relies on subjective interpretation of ultrasonographic images. A cross-sectional study was conducted to develop an objective ultrasonographic parameter for sylvian fissure evaluation. Using 3D ultrasound with multiplanar display, the sylvian fissure-to-parietal bone distance (SPB) was measured from the midpoint to the inner surface of the parietal bone, perpendicular to the falx cerebri. The results of this study demonstrated that the SPB can be reproducibly measured from 12 weeks of gestation to term, and that there was a strong positive correlation between the SPB and gestational age. This parameter may be useful in the prenatal diagnosis of abnormal cerebral sulcation.[unreadable] [unreadable] 6. Quantitative assessment of gestational sac shape. The use of 3D ultrasound in obstetrics allows the capture of the entire volume of small objects, such as the gestational sac and small placentas. Morphological and quantitative analysis of the gestational sac may provide baseline parameters for studying patients at risk for early pregnancy failure. However, volume information requires location of the object's surface so that its volume can be defined. This year we developed a quantitative method for characterizing the gestational sac shape with a single number, called the gestational sac shape score. The 3D coordinates of surface-point sets were obtained in 20 first-trimester gestational sacs in normal pregnancies. Cubic spline interpolation was used to determine the coordinates of a standard surface-point sample (3,660) for each sac in each slice sample, giving to each sac a standard configuration by moving its center of gravity to the origin, aligning its inertial axes along the coordinate axes. Cubic spline interpolations were accurate in most cases, with means close to 0%, and approximately 95% of the errors being less than 10%. This approach provides quantitative shape information about a variety of biological shapes (e.g. gestational sac) and how they change over time.